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Protein Integrated Network Analysis to Reveal Potential Drug Targets Against Extended Drug-Resistant Mycobacterium tuberculosis XDR1219

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Abstract

The reconstruction and analysis of the protein–protein interaction (PPI) network is a powerful approach to understand the complex biological and molecular functions in normal and disease states of the cell. The interactome of most organisms is largely unidentified except some model organisms. The current study focused on the construction of PPI network for the human pathogen Mycobacterium tuberculosis (MTB)-resistant strain XDR1219 using computational methods. In this work, a bioinformatics approach was employed to reveal potential drug targets. The pipeline adopted the combination of an extensive integrated network analysis that led to identify 22 key proteins involved in drug resistance, resistant metabolic pathways, virulence, pathogenesis and persistency of the infection. The MTB XDR1219 interactome consists of 11,383 non-redundant PPIs among 1499 proteins covering 38% of the entire MTB XDR1219 proteome. The overall quality of the network was assessed and topological parameters of the PPI were calculated. The predicted interactions were functionally annotated and their relevance was assessed with the functional similarity. The study attempts to present the interactome of previously unidentified MTB XDR1219 and revealed potential drug targets that can be further explored by scientific community.

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Funding

Funding was provided by Pakistan Science Foundation (Grant No. Med 431) and International Foundation for Science (Grant No. I-1-F-5378-2).

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  1. Lab 103 PCMD ext. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Noor ul Ain Zahra, Faiza Jamil & Reaz Uddin

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  1. Noor ul Ain Zahra
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Zahra, N.u.A., Jamil, F. & Uddin, R. Protein Integrated Network Analysis to Reveal Potential Drug Targets Against Extended Drug-Resistant Mycobacterium tuberculosis XDR1219. Mol Biotechnol 63, 1252–1267 (2021). https://doi.org/10.1007/s12033-021-00377-w

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